1. Field of the Invention
This invention relates to fluorocarbon chain linking arms and their use in conjugating haptens or drugs to carriers.
An antigen is a substance which may be recognized by an antibody. An antigen that elicits a response from the immune system is called an immunogen. Macromolecular molecules such as proteins or nucleic acids are usually immunogenic in a xenogeneic host; molecules with a molecular weights less than 5000 are usually not. However, many small non-immunogenic substances will stimulate an immune response if covalently attached to a large carrier molecule; such substances are termed haptens. A hapten can be recognized and bound by an antibody even though it cannot stimulate antibody production itself. Linking a haptenic substance to carriers results in a molecule generally referred to as synthetic antigen. This invention relates to a novel linker connecting the synthetic antigens with hapten to its carrier.
Several linking arms are known for conjugating haptens to carriers. See Kolar U.S. Pat. No. 4,442,284; Lemieux U.S. Pat. No. 4,137,401; Feizi U.S. Pat. No. 4,563,445; Svenska Sockerfabrike, EP Appl 98,252; Behringerwerke AG, EP Appl 60,999. None of these linking arms, however, contain fluorocarbon chains.
An extensive review of methods of fluorinating organic compounds and of uses of fluorinated organic compounds appears in Gerstenberger and Haas, Angew. Chem. Int. Ed. Engl , 20: 647-667 (1981), incorporated by reference herein. Nowhere does it even suggest that fluorinated compounds have utility as "spacers" in immunological conjugates.
Klevens U.S. Pat. No. 3,133,908, teaches binding fluorinated aliphatic acids, alcohols and their derivatives or amines to a proteinaceous material to protect the latter from denaturation. He does not, however, disclose use of the fluorinated compound as a bridging agent.
Ponpipom U.S. Pat. No. 4,259,324 describes an "immunologic adjuvant" having the structure Y-R, where Y is one of three thio glycosides and R may be 3-[(p-tetrafluorophenethyl) phenyl] propyl. This side chain is not used to couple the glycoside to another molecule. See also Ponpipom U.S. Pat. No. 4,301,152 and U.S. Pat. No. 4,228,274.
Bovin, Chemical Abstracts Selects Carbohydrates (chemical Aspects), 106: 102617f teaches a synthesis of a T-antigen disaccharide with an --0(CH.sub.2).sub.3 NHCOCF.sub.3 moiety, without disclosing use of this moiety as a linker. Moreover, only one carbon atom is fluorinated.
One of the glycosides described in Svenska Sockerfabrike, EP Appl 98,252 is EQU (sugar).sub.1-10 --O--(CH.sub.2).sub.2-20 -Hal
(see page 7). This compound is used as an intermediate in the preparation of various O-glycosides. There is no disclosure of use of this omega-haloalkyl glycoside as a linking arm. Only one carbon atom is fluorinated.
Duschinsky and Pleven, Heidelberger, J. Amer. Chem. Soc., 79: 4559 (1957) describe the preparation of 5-fluoropyrimidines.
Gottwald, et al., J. Biol Chem., 239: 435 (1964) discuss the chemical synthesis and enzyme-inhibitory activity of alpha-monofluoroglutaric acid.
Gilad, U.S. Pat. No. 4,433,051, refers to alphadifluoromethylornithine derivatives.
No admission is made that any of the foregoing constitute more than information which applicants thought might be of interest to an examiner.